Cytokines are hormone-like factors that are active in regulating the survival, growth, differentiation and activity of various types of cells. Numerous cytokines have been described, and some of their functions elucidated. Several cytokines appear to be important in hematopoiesis, the process whereby pluripotent hematopoietic stem cells give rise to highly differentiated, mature blood cells that perform very specific functions (reviewed in Metcalf, D. 1984. The Hemopoietic Colony Stimulating Factors. Elsevier, Amsterdam, 486 pp). Cytokines designated "Interleukins" influence immune effector cells.
OX40 is a membrane glycoprotein with an approximate M.sub.r of 47-51 Kd that is present on the CD4+ subset of activated rate T cells (Paterson et al., Mol. Immunol. 24:1281; 1987). Mallett et al. (EMBO J. 9:1063, 1990) report the cloning and characterization of OX40, and the similarity of this membrane glycoprotein to the low affinity nerve growth factor receptor (NGFR). NGFR and OX40 are members of a superfamily of cell surface proteins defined by the presence of cysteine-rich motifs in the extracellular region (Mallett and Barclay, Immunology Today 12:220; 1991). This superfamily includes the B cell antigen CD40, the lymphocyte antigen CD27, CD30 (an antigen found on Hodgkin's lymphoma and Reed-Sternberg cells), two receptors for Tumor Necrosis Factor (TNF), a murine protein referred to as 4-1BB, and proteins encoded by the T2 open reading frame (ORF) of Shope fibroma virus (along with the equivalent proteins from other pox viruses) (Smith et al., Biochem. Biophys. Res. Commun. 176:335; 1991).
Prior to the present invention, a ligand for OX40 was unknown. Accordingly, there is a need in the art to identify and characterize an OX40 ligand (OX40-L).